1. Field of the Invention
This invention provides an improved process for cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy] ethyl}pyrrolidine which is an intermediate for the preparation of (-)cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro naphthalene-2-ol which is useful for the treatment of osteoporosis.
2. Description of the Related Art
A preparation of (-)cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro naphthhalene-2-ol is described in U.S. Pat. No. 5,552,241 which is hereby incorporated by reference. This compound is an estrogen agonist and is useful for treatment of conditions caused by estrogen difficiency. U.S. Pat. No. 5,552,241 also describes the synthesis of cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy] ethyl}pyrrolidine by hydrogeneration of nafoxidine.
Lednicer, et al., J. Med. Chem., 12, 881 (1969) described estrogen antagonists of the structure ##STR1##
wherein R.sup.2 is phenyl or cyclopentyl and R.sup.3 is H, ##STR2##
or --CH.sub.2 CHOHCH.sub.2 OH.
Bencze, et al., J. Med. Chem., 10, 138 (1967) prepared a series of tetrahydronaphthalenes intended to achieve separation of estrogenic, antifertility and hypocholesterolemic activities. These structures are the general formula ##STR3##
wherein R.sup.1 is H or OCH.sub.3 ; R.sup.2 is H, OH, OCH.sub.3, OPO(OC.sub.2 H.sub.5).sub.2, OCH.sub.2 CH.sub.2 N(C.sub.2 H.sub.5).sub.2, OCH.sub.2 COOH or OCH(CH.sub.3)COOH.
U.S. Pat. No. 3,234,090 refers to compounds which have estrogenic and antifungal properties of the formula ##STR4##
in which Ph is a 1,2-phenylene radical, Ar is a monocyclic carbocyclic aryl group substituted by tertiary amino-lower alkyl-oxy, in which tertiary amino is separated from oxy by at least two carbon atoms, R is hydrogen, an aliphatic radical, a carbocyclic aryl radical, a carbocyclic aryl-aliphatic radical, a heterocyclic aryl radical or a heterocyclic aryl aliphatic radical, the group of the formula --(C.sub.n H.sub.2n-2)-- stands for an unbranched alkylene radical having from three to five carbon atoms and carrying the groups Ar and R, salts, N-oxides, salts of N-oxides or quaternary ammonium compounds thereof, as well as procedure for the preparation of such compounds.
U.S. Pat. No. 3,277,106 refers to basic ethers with estrogenic, hypocholesterolemic and antifertility effects which are of the formula ##STR5##
in which Ph is a 1,2-phenylene radical, Ar is a monocyclic aryl radical substituted by at least one amino-lower alkyl-oxy group in which the nitrogen atom is separated from the oxygen atom by at least two carbon atoms, R is an aryl radical, and the portion --(C.sub.n H.sub.2n-2)-- stands for lower alkylene forming with Ph a six- or seven-membered ring, two of the ring carbon atoms thereof carry the groups Ar and R, salts, N-oxides, salts of N-oxides and quaternary ammonium compounds thereof.
Lednicer, et al., in J. Med. Chem. 10, 78 (1967) and in U.S Pat. No. 3,274,213 refer to compounds of the formula ##STR6##
wherein R.sub.1 and R.sub.2 are selected from the class consisting of lower alkyl and lower alkyl linked together to form a 5 to 7 ring member saturated heterocyclic radical. References
1. Kanapure, S. P.; Das, K. G.; Bhawal, B. M. Synth. Comm. 1984, 14,1205-1211. PA0 2. Lexa, D.; Saveant, J. M.; Zickler, J. J. Amer. Chem. Soc. 1977, 99, 2786-2790. PA0 3. Chan, T. H.; Brook, M. A.; Chaly, T. Synthesis 1983, 203-205. PA0 4. Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.; Laberge, L.; Rousell, J. Tet. Lett. 1986, 27, 279-282. PA0 5. McMurry, J. E.; Kees, K. L. J. Org. Chem. 1977, 42, 2655-2656.